MiR-21-5p but not miR-1-3p expression is modulated by preconditioning in a rat model of myocardial infarction
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ORIGINAL ARTICLE
MiR-21-5p but not miR-1-3p expression is modulated by preconditioning in a rat model of myocardial infarction Annika Raupach1 · Carolin Torregroza1 · Julia Niestegge1 · Katharina Feige1 · Swantje Klemm‑Meyer1 · Inge Bauer1 · Timo Brandenburger1 · Hilbert Grievink2 · André Heinen3 · Ragnar Huhn1 Received: 19 May 2020 / Accepted: 2 August 2020 © The Author(s) 2020
Abstract Isoflurane (Iso) preconditioning (PC) is known to be cardioprotective against ischemia/reperfusion (I/R) injury. It was previously shown that microRNA-21-5p (miR-21-5p) is regulated by Iso-PC. It is unclear, if expression of cardiac enriched miR1-3p is also affected by Iso-PC, and associated with activation of HIF1α (hypoxia-inducible factor 1-alpha). Male Wistar rats (n = 6–8) were randomly assigned to treatment with or without 1 MAC Iso for 30 min, followed by 25 min of regional myocardial ischemia, with 120 min reperfusion. At the end of reperfusion, myocardial expression of miR-1-3p, miR-21-5p and mRNAs of two HIF-1α-dependent genes, VEGF (vascular endothelial growth factor) and HO-1 (heme oxygenase-1), were determined by quantitative PCR. Protein expression of a miR-21 target gene, PDCD4 (programmed cell death protein 4), was assessed by western blot analysis. Infarct sizes were analyzed with triphenyltetrazoliumchloride staining. MiR-21-5p expression was increased by Iso, whereas expression of miR-1-3p was not altered. The expression of VEGF but not HO-1 was induced by Iso. Iso-PC reduced infarct sizes compared to untreated controls. No regulation of miRNA and mRNA expression was detected after I/R. PDCD4 protein expression was not affected after Iso exposure. Expression of miR-21-5p, in contrast to miR-1-3p, is altered during this early time point of Iso-PC. HIF1α signaling seems to be involved in miR-21-5p regulation. Keywords Isoflurane · Preconditioning · miR-1-3p · miR-21-5p · HIF1α
Introduction Cardiac diseases are the leading cause of death in the United States [1] and are initiated or often accompanied by ischemia-reperfusion (I/R) injury. Murry et al. discovered that short intervals of I/R prior to global ischemia reduce I/R injury [2], a phenomenon named ischemic preconditioning (IPC). The effect of IPC can be mimicked pharmacologically. Volatile anesthetics, like isoflurane (Iso), show cardioprotective effects via reducing infarct size in in vivo models [3, 4]. * Carolin Torregroza [email protected]‑duesseldorf.de 1
Department of Anesthesiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany
2
Cyclotron/Radiochemistry/MicroPET Unit, Hadassah Hebrew University Hospital, 91120 Jerusalem, Israel
3
Department of Cardiovascular Physiology, Heinrich-Heine-University Duesseldorf, Universitaetsstr. 1, 40225 Duesseldorf, Germany
The underlying mechanisms of preconditioning (PC) are yet not fully understood. Evidence suggests, that microRNAs (miRNAs), a class of small non coding RNAs, serve as mediators for preconditioning and influence the protective effect of precon
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